Nodular lymphocyte-predominant Hodgkin’s lymphoma

Lymphocyte-predominant Hodgkin’s lymphoma (LPHL) differs in histologic and clinical presentation from classical Hodgkin’s lymphoma (cHL). Treatment of LPHL patients using standard Hodgkin’s lymphoma protocols leads to complete remission in more than 95% of patients. Survival and freedom from treatment failure are substantially worse in advanced-stage patients than for early-stage patients. Thus, patients in advanced stages and those in early stages with unfavorable risk factors should be treated similar to those with cHL. In contrast, patients with early-stage LPHL without risk factors might be sufficiently treated with reduced-intensity programs having less severe adverse effects. As a result, treatment of early LPHL is rather heterogeneous, including radiotherapy using extended-fleld technique, involved-fleld radiotherapy (IF-RT), combined-modality treatment, and, more recently, monoclonal antibodies. Watch-and-wait strategy plays an important role in pediatric oncology, to avoid adverse effects associated with therapy. IF-RT seems to be emerging as a treatment of choice for patients with stage IA LPHL; most larger study groups, such as the German Hodgkin Study Group and the European Organisation for Research and Treatment of Cancer, have adopted IF-RT as the treatment of choice for these patients.     

Photodynamic therapy mediated induction of accelerated re-endothelialisation following injury to the arterial wall: implications for the prevention of postinterventional restenosis.

OBJECTIVE: Accelerated re-endothelialisation may inhibit the development of restenosis. Basic Fibroblast Growth Factor (bFGF) plays a key role for early proliferative activity in the artery following injury. Therefore, this study was devised to examine the effect of photodynamic therapy (PDT) on post-injury re-endothelialisation in vivo, and bFGF-mRNA expression in endothelial cells (EC) in vitro. MATERIALS AND METHODS: Rat carotid arteries were balloon-injured prior to PDT. Arteries were analysed after 1, 3, 5, 14 and 30 days. Morphometric measurements were undertaken following injection of 0.5% Evans Blue which stains non-endothelialised surfaces only. To identify EC, immunohistochemistry (CD-31) was performed. Proliferation was assessed by fluorescence cell counting. PCR quantification of bFGF-mRNA expression and proliferation were assessed in bovine aortic EC which were plated on isolated, PDT-treated EC-derived extracellular matrix at (12), 24, 48 (72 h). RESULTS: Three days following PDT, arteries displayed significantly increased endothelial lining (p = 0.02), which was more pronounced at 5 (p = 0.03) and 14 days (p = 0.02). At 30 days no relevant differences between PDT and control were noted. EC proliferation on PDT-treated matrix was significantly increased at 24, 48, and 72 h (p = 0.0004), whereas bFGF-mRNA expression was significantly increased at 24 h only (p = 0.007). CONCLUSION: Post-injury PDT appears to accelerate re-endothelialisation. Expression of bFGF-mRNA, however, although increased shortly after PDT, may not be responsible for a constant stimulation of EC proliferation.     

Sp?tsch?den nach Behandlung des Hodgkin-Lymphoms

Im Hinblick auf die eindrucksvollen Remissionsraten, die in den letzten Jahren in der Therapie des Hodgkin-Lymphoms erzielt wurden, gewinnen die therapieinduzierten Spätkomplikationen einen immer größeren Stellenwert. In Abhängigkeit von Stadium und Risikofaktoren können nach der Primärtherapie mittlerweile Langzeitremissionen von über 80% erzielt werden. Demzufolge hat gerade das Überleben junger Patienten im reproduktiven Alter zugenommen, weshalb genaue Analysen therapieinduzierter Spätfolgen immer mehr in den Vordergrund treten. Zu den wichtigsten therapieinduzierten Akut- und Spättoxizitäten zählen Infertilität, kardiale, pulmonale oder thyroidale Funktionsstörungen und insbesondere Sekundärneoplasien, die zu einer signifikanten Mortalität beitragen. Außerdem kann ein noch lange Zeit nach der Therapie anhaltendes Fatiguesyndrom auftreten. Die Therapiestrategien aktueller klinischer Studien zielen daher insbesondere auf eine Reduktion von therapiebedingten Spätfolgen bei gleichzeitiger Beibehaltung der guten Tumorkontrolle.     

Transthoracic esophagectomy and lobectomy performed in a patient with synchronous lung cancer and combined esophageal cancer and esophageal leiomyosarcoma.

We report a pitfall deriving from the assumption of metastatic disease based upon seemingly identical histology in a pulmonary lesion and in the esophagus. In a 60-year-old patient, cT1 esophageal squamous cell carcinoma was found. One of the two pulmonary nodules was histologically diagnosed as metastasis. When esophageal perforation occurred during palliative therapy, esophagectomy became necessary together with the right lower lobectomy for the removal of the remaining pulmonary lesion. Definitive histology showed pT1N0 cancer of the esophagus, primary esophageal sarcoma and pT4N0 bronchogenic carcinoma. The other pulmonary lesion was re-evaluated and defined as intralobar M1 of bronchogenic carcinoma.     

Growth of Hodgkin cell lines in severely combined immunodeficient mice.

No animal model exists for the in vivo growth of Hodgkin's-lymphoma-derived cells. Neither unmanipulated Hodgkin's-disease(HD)-derived cell lines nor primary biopsy tissue could be grown in nude mice. Since the severe combined immunodeficient (SCID) mouse has been reported to be a better recipient for transplanted human lymphatic tissue than the nude mouse, we tested whether SCID mice provide suitable conditions for the in vivo growth of HD cell lines. Tumorigenicity of HD cells was tested in untreated and pre-treated SCID mice and in another combined immunodeficient mouse strain, beige/nude/X-linked immunodeficient (BNX) mouse. SCID mice supported in vivo growth of the 6 HD cell lines tested (L428, L540, L591, DEV, HD-LM2, KM-H2). Only one of the 6 lines (DEV) was tumorigenic in BNX mice. No HD cell line proliferated in T-cell-deficient nude mice. Thus, in vivo growth of HD cell lines appeared to be related to the degree of host immunodeficiency. Additional growth supportive treatments such as fibrosarcoma co-transplantation, intraperitoneal mineral oil injection or immunosuppressive pre-treatment (anti-asialo-GMI-antibody injection) permitted growth of 3 additional HD cell lines in BNX mice. The immunophenotype and karyotype of explanted graft cells were identical to the original cell lines. Our experiments describe an effective and reproducible xenograft model for growth of Hodgkin's-disease-derived cell lines. This may be of value for elucidating the growth characteristics of Hodgkin's-lymphoma-derived cells as well as for testing new therapeutic regimens.     

Amyloid fibril formation by human stefin B: influence of pH and TFE on fibril growth and morphology.

As shown before, human stefin B (cystatin B) populates two partly unfolded species, a native-like state at pH 4.8 and a structured molten globule state at pH 3.3 (high ionic strength), from each of which amyloid fibrils grow. Here, we show that the fibrils obtained at pH 3.3 differ from those at pH 4.8 and that those obtained at pH 3.3 (protofibrils) do not transform readily to mature fibrils. In addition we show that amorphous aggregates are also a source of fibrils. The kinetics of amyloid fibril formation at different trifluoroethanol (TFE) concentrations were measured. TFE accelerates fibril growth at predenaturational concentrations of the alcohol. At concentrations higher than 10%, the fibrillar yield decreases proportionately as the population of an all alpha-helical, denatured form of the protein increases. At an optimum TFE concentration, the lag and the growth phases are observed, similarly to some other amyloidogenic proteins. Morphology of the protein species at the beginning and the end of the reactions was observed using atomic force microscopy and transmission electron microscopy. Final fibril morphologies differ depending on solvent conditions.     

Enzyme-linked immunosorbent assay for Escherichia coli heat-stable enterotoxin.

The sensitivity of an enzyme-linked immunosorbent assay (ELISA) to detect pure native Escherichia coli heat-stable toxin (ST) and to identify ST-producing strains among clinical isolates was determined. Two synthetically produced ST preparations were used to raise hyperimmune antisera in rabbits and goats: ST(S), which has the same antigenicity as native ST; and ST(C), which is 15-fold more immunogenic. These antisera were used in the double-sandwich technique as either crude double-species antisera or pure single-species antibody. The sensitivity of the assay was increased by using either a purer antibody preparation or the antiserum to the more potent immunogen; the assay in which pure antibody to ST(C) was used was 2,857-fold more sensitive in detecting ST than the assay in which crude antiserum to ST(S) was used. The minimum amount of ST detectable by the ST(C) ELISA was 140 pg/ml, which was an amount 285-fold smaller than that detectable by the suckling mouse assay. Among 50 human E. coli isolates examined by both the ST(C) ELISA and an ELISA for heat-labile toxin (LT), which had a sensitivity of 290 pg/ml for LT, the respective toxins were consistently identified in broth cultures of 10 LT+ and ST-, 15 LT+ and ST+, and 10 LT- and ST+ strains, and there were no false-positive responses. The ST(C) ELISA also detected ST in all of seven ST - producing E. coli strains tested of human origin, which had been shown elsewhere by DNA hybridization probes to have ST-coding genes of either human or porcine origin, and in all of three ST-producing E. coi strains tested of porcine origin. These results indicate that the sensitivity of the ST(C) ELISA is the same as that of previously described LT ELISAs. The concomitant use of both ST and LT ELISAs provides a rapid, simple, and sensitive method for identifying among clinical isolates enterotoxigenic strains of E. coli which produce either toxin.